1. Field of the Invention
The present invention relates to an automated sample extractor or feeder/inoculator and a removable manual override operator for a vessel or conduit. This vessel or conduit can be a bioreactor or other similar equipment.
2. Description of the Background Art
Development of new or more efficient commercialization of existing products requires faster and more effective methods to measure process variables. This is particularly true in processes which require cell culture and fermentation processes conducted in bioreactors where the accuracy of measurements in the research and development are critical for achieving economic production of high purity and highly refined end products.
Some factors which must be controlled include temperature and pressure. These factors are easily measured by utilizing standard sensors. However, many other factors can be measured only by removing samples for external laboratory analysis. The frequency of sample extraction for testing and measurement, number of tests on each sample and the time constraints on the process vary widely as do the methods and equipment used to obtain the samples.
In most cases, measurement processes for variables do not lend themselves to in-situ measurement by remote sensors directly in the process. Instead, samples must be physically extracted from the process and examined and manipulated outside the vessel or conduit. Before this examination and manipulation process can be carried out, a safe, effective means of sample extraction must be made available. By "safe" here we mean that the process should remain as unaffected by the act of taking a sample as possible as the sample itself should. Besides being safe and effective, the means of sample removal should also take into consideration that the character of sample material taken from one place is very likely to differ from that taken from another place. Therefore, it is important to provide a means by which sample material can be removed from the vessel from a location where its character correlates well with information being derived from insitu sensor measurements as well as with the character of the bulk of the process material. As such the means for removing material would best be one that also can be flexibly incorporated new or existing systems such as into existing (angled) ferrules and, at the same time, provide a means of sampling the process in the same area as is sampled by other in-situ measurement sensors.
The prior art provides for removal of sample material but does not provide features that could adequately address issues concerning the quality of the material as a representative sample of the process nor the ability to be effectively incorporated into existing system. Many of the prior art designs do not lend themselves easily to use as a retrofit but, instead, require substantial modification to the system for installation or repositioning. An apparatus should minimize or eliminate the dangers associated with the sampling process in an efficient and cost effective manner while providing quality, reproducible results in order to be of value for commercial application.
When working with samples, especially hazardous samples, it is necessary to remove or feed/inoculate material without endangering the integrity of the process, subsequently sampled material, the operator or the outside environment. Many prior art devices are unsatisfactory in this area.
Also, some prior art systems are not automated. Therefore, there is potential danger posed by human procedural errors which could easily result in operator and environmental exposure. Accordingly, a need exists for an automatable apparatus with the capacity for independent verification of equipment operation built in.
There is a need for an automated system which offers a quick, easy-to-use means to override the automation apparatus. Sampling is most important in processes of which relatively little is known. The apparatus should be one that is easily incorporated into new and existing systems in one or more places in a cost-effective way, allowing material to be removed or added to the process at multiple points so that the optimal means for monitoring and controlling the process can be established. Once defined, unnecessary or redundant devices should be easily removed from the process without adversely affecting the process but these devices should, ideally also remain intact and unaffected so that they may be readily used again in other process development, monitoring and control applications.
There always is a need to collect unanticipated samples. In providing this means, it is critical that the apparatus should be able to provide essentially identical samples in either case (i.e. manual or automated mode). Furthermore, the materials being sampled themselves are often expensive. Therefore, excessive removal of sample should be avoided. In the existing art, rotating cams and rotating knobs or handwheels are usually the means employed to open and close sampling valves. These designs require the operator to move their arm or, at least their hand, through a range of motion of 90-180 degrees or more. In the very best conditions this motion will take at least 1.0 second to perform a full cycle (open and close) Since most sample port apertures are 5 mm or more in diameter, it is very likely that 30 ml or more of process material will flow out between the time the valve is opened and closed. Usually the volume of sample required is small, often 50 ml or less.
As a consequence, one of two events occurs. Either a relatively large amount of sample material is wasted or the technician must resort to "throttling" the valve (partially opening it). Since process material is either valuable, hazardous or there is a need for cleanliness, there is a tendency of technicians to resort to throttling the valve to more carefully and accurately control the flow of sampling material. However, "throttling" can significantly alter the sample in two important ways.
First, the smaller, more fluid elements of the sample will more easily pass through the constricted opening rather than the larger, more viscous elements. The result is a selective removal, or sieving out, of the larger, more viscous elements from the sample.
Second, those elements that do pass through the crevice will have been subjected to high levels of shear, possibly significantly altering their physical and chemical properties, changing them from the desired representative subsample of process populations and conditions.
An effective means to minimize this effect will require the valve to be opened to a full open position until enough sample is drawn at which time the valve must be rapidly closed. Automated actuation using electromagnetic solenoids or pneumatic actuators which have only two position, "open" or "closed", are much more preferable over "throttling" or "positioning" actuators.
Likewise, to eliminate sample bias in a manually operated valve, a manual motion which can be rapidly translated into full articulation of the operating rod from fully "closed" to fully "opened" and back must be realized. The fastest (articulating) elements in humans, besides the eyes, are the fingers. A "flick" or "snap" of the fingers takes a fraction of a second. Since most sample particles are much smaller than the range of motion used in a single flick of a finger, direct coupling of finger motion to actuation of the operating rod of the sampling valve presents an effective solution. Furthermore, because of the relatively small cross sectional area of sampling orifice and the relatively moderate pressures used in most (biological) manufacturing processes, little or no gear reduction will be required to overcome the tension of a "fail close" return spring operating on valve operating rod to close and form a seal at the orifice. The mechanism described here can easily and quickly be removably connected to valves with automated mechanisms. When manual sampling is necessary, trigger-action control can provide a more physically and chemically representative subsample of the process with more precise control of sampling volumes with less wasting of material.
When removing or adding material to a process, it is often desirable to maintain the aseptic integrity of the process as well as protect the surrounding environment. As such it is important that material from the previous removal or addition operation not contaminate the environment, the process or the current sample material. Loss of a sample run or contamination of the process can have extremely expensive ramifications. Therefore, it is important to add material or obtain a sample without the procedure causing contamination.
Many prior art devices permit accumulation or pooling of samples or cleansing medium. When the device is first used this may not create a problem; however, upon subsequent runs, the sample material or material added to the process through the device may be contaminated, or at least, diluted.
Additionally in the prior art, technology used for taking samples is generally unsatisfactory for feeding/inoculating the vessel or container.